Age-related Metabolic Changes Research Articles

An Analysis of Age-Related Body Composition Changes and Metabolic Patterns in Korean Adults Using FDG-PET/CT Health Screening Data.

F-18-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) can be used to measure bone mineral density (BMD), cross-sectional muscle area (CSMA), Hounsfield units (HU) of liver and muscle, subcutaneous adipose tissue (SAT), abdominal visceral adipose tissue (VAT), and glucose metabolism. The present study aimed to identify age-related changes in body composition and glucose metabolism in Korean using opportunistic FDG-PET/CT imaging. We analyzed FDG-PET/CT, clinical history, and laboratory data abstracted from the medical records of patients who underwent health screening at a single institute between 2017 and 2022. In total, 278 patients were included in the analysis (male:female=140:138). Age and body mass index were positively correlated in female, but negatively correlated in male. BMD decreased with age more in female, and CSMA decreased with age more in male. Muscle HU decreased with age for both sexes. In female, SAT and VAT increased with age; and in male, SAT decreased slightly while VAT remained stable. Muscle glucose metabolism showed no association with age in male but increased with age in female. CSMA correlated positively with BMD overall; and positively correlated with VAT and SAT in male only. In female only, both SAT and VAT showed negative correlations with glucose metabolism and correlated positively with muscle glucose metabolism. Liver HU values were inversely correlated with VAT, especially in female; and positively correlated with muscle glucose metabolism in female only. FDG-PET/CT demonstrated distinct patterns of age-related changes in body composition and glucose metabolism, with significant differences between sexes.

Synaptic mitochondria glycation contributes to mitochondrial stress and cognitive dysfunction.

Mitochondrial and synaptic dysfunction are pathological features of brain aging and cognitive decline. Synaptic mitochondria are vital for meeting the high energy demands of synaptic transmission. However, little is known about the link between age-related metabolic changes and the integrity of synaptic mitochondria. To this end, we investigate the mechanisms of advanced glycation endproducts (AGEs)-mediated mitochondrial and synaptic stress and evaluate the strategies to eliminate these toxic metabolites. Using aged brain and novel transgenic mice overexpressing neuronal glyoxalase 1 (GLO1), we comprehensively analyzed alterations in accumulation/buildup of AGEs and related metabolites in synaptic mitochondria and the association of AGE levels with mitochondrial function. We demonstrate for the first time that synaptic mitochondria are an early and major target of AGEs and the related toxic metabolite methylglyoxal (MG), a precursor of AGEs. MG/AGEs-insulted synaptic mitochondria exhibit deterioration of mitochondrial and synaptic function. Such accumulation of MG/AGEs positively correlated with mitochondrial perturbation and oxidative stress in aging brain. Importantly, clearance of AGEs-related metabolites by enhancing neuronal GLO1, a key enzyme for detoxification/of AGEs, reduces synaptic mitochondrial AGEs accumulation and improves mitochondrial and cognitive function in aging and AGE-challenged mice. Furthermore, we evaluated the direct effect of AGEs on synaptic function in hippocampal neurons in live brain slices as an ex-vivo model and in vitro cultured hippocampal neurons by recording long-term potentiation (LTP) and measuring spontaneously occurring miniature excitatory postsynaptic currents (mEPSCs). Neuronal GLO1 rescues deficits in AGEs-induced synaptic plasticity and transmission by fully recovery of decline in LTP or frequency of mEPSC. These studies explore crosstalk between synaptic mitochondrial dysfunction and age-related metabolic changes relevant to brain aging and cognitive decline. Synaptic mitochondria are particularly susceptible to AGEs-induced damage, highlighting the central importance of synaptic mitochondrial dysfunction in synaptic degeneration in age-related cognitive decline. Thus, augmenting GLO1 function to scavenge toxic metabolites represents a therapeutic approach to reduce age-related AGEs accumulation and to improve mitochondrial function and learning and memory.

MICOS Complex Loss Governs Age-Associated Murine Mitochondrial Architecture and Metabolism in the Liver, While Sam50 Dictates Diet Changes.

The liver, the largest internal organ and a metabolic hub, undergoes significant declines due to aging, affecting mitochondrial function and increasing the risk of systemic liver diseases. How the mitochondrial three-dimensional (3D) structure changes in the liver across aging, and the biological mechanisms regulating such changes confers remain unclear. In this study, we employed Serial Block Face-Scanning Electron Microscopy (SBF-SEM) to achieve high-resolution 3D reconstructions of murine liver mitochondria to observe diverse phenotypes and structural alterations that occur with age, marked by a reduction in size and complexity. We also show concomitant metabolomic and lipidomic changes in aged samples. Aged human samples reflected altered disease risk. To find potential regulators of this change, we examined the Mitochondrial Contact Site and Cristae Organizing System (MICOS) complex, which plays a crucial role in maintaining mitochondrial architecture. We observe that the MICOS complex is lost during aging, but not Sam50. Sam50 is a component of the sorting and assembly machinery (SAM) complex that acts in tandem with the MICOS complex to modulate cristae morphology. In murine models subjected to a high-fat diet, there is a marked depletion of the mitochondrial protein SAM50. This reduction in Sam50 expression may heighten the susceptibility to liver disease, as our human biobank studies corroborate that Sam50 plays a genetically regulated role in the predisposition to multiple liver diseases. We further show that changes in mitochondrial calcium dysregulation and oxidative stress accompany the disruption of the MICOS complex. Together, we establish that a decrease in mitochondrial complexity and dysregulated metabolism occur with murine liver aging. While these changes are partially be regulated by age-related loss of the MICOS complex, the confluence of a murine high-fat diet can also cause loss of Sam50, which contributes to liver diseases. In summary, our study reveals potential regulators that affect age-related changes in mitochondrial structure and metabolism, which can be targeted in future therapeutic techniques.

Multifaceted role of erlotinib in various cancer: nanotechnology intervention, patent landscape, and advancements in clinical trials.

Erlotinib (ELB) is a tyrosine kinase inhibitor that targets the activity of Epidermal Growth Factor Receptor (EGFR) protein found in both healthy and cancerous cells. It binds reversibly to the ATP-binding site of the EGFR tyrosine kinase. ELB was approved by the US Food and Drug Administration (FDA) in 2004 for advanced non-small cell lung cancer (NSCLC) treatment in patients who relapsed after at least one other therapy. It was authorized for use with gemcitabine in 2005 for the treatment of advanced pancreatic cancer. In addition to lung cancer, ELB has shown promising results in the treatment of other cancers, including breast, prostate, colon, pancreatic, cervical, ovarian, and head and neck cancers. However, its limited water solubility, as a BCS class II drug, presents biopharmaceutical problems. Nanoformulations have been developed to overcome these issues, including increased solubility, controlled release, enhanced stability, tumor accumulation, reduced toxicity, and overcoming drug resistance. In older patients, ELB management should involve individualized dosing based on age-related changes in drug metabolism and close monitoring for adverse effects. Regular assessments of renal and hepatic functions are essential. This review provides an overview of ELB's role of ELB in treating various cancers, its associated biopharmaceutical issues, and the latest developments in ELB-related nanotechnology interventions. It also covers ELB patents granted in previous years and the ongoing clinical trials.

Differential impacts of nonsteroidal anti-inflammatory drugs on lifespan and healthspan in aged Caenorhabditis elegans.

Aging and age-related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown their promise in mitigating age-related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age-related changes in drug metabolism and tolerance, which could result in age-dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk-1/skn-1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk-1 was knocked out in the pmk-1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age-dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.

Ferroptosis and aerobic training in ageing.

Ferroptosis is a form of programmed cell death that plays a significant role in causing several diseases such as heart attack and heart failure, through alterations in fat, amino acid, and iron metabolism. Comprehending the regulatory mechanisms of ferroptosis signaling is critical because it has a considerable effect on the elderly's mortality. Conversely, age-related changes in substrate metabolism and metabolite levels are recognized to give rise to obesity. Furthermore, research has proposed that aging and obesity-related changes in substrate metabolism may aggravate ferroptosis. The suppression of ferroptosis holds potential as a successful therapeutic approach for managing different diseases, including sarcopenia, cardiovascular diseases, and central nervous system diseases. However, the pathologic and biological mechanisms behind the function of ferroptosis are not fully comprehended yet. Physical activity could affect lipid, amino acid, and iron metabolism to modulate ferroptosis. The aim of this study is to showcase the current understanding of the molecular mechanisms leading to ferroptosis and discuss the role of aging and physical activity in this phenomenon.

Millifluidic magnetophoresis-based chip for age-specific fractionation: evaluating the impact of age on metabolomics and gene expression in yeast.

A novel millifluidic process introduces age-based fractionation of S. pastorianus var. carlsbergensis yeast culture through magnetophoresis. Saccharomyces yeast is a model organism for aging research used in various industries. Traditional age-based cell separation methods were labor-intensive, but techniques like magnetic labeling have eased the process by being non-invasive and scalable. Our approach introduces an age-specific fractionation using a 3D-printed millfluidic chip in a two-step process, ensuring efficient cell deflection in the magnetic field and counteracting magnetic induced convection. Among various channel designs, the pinch-shaped channel proved most effective for age differentiation based on magnetically labeled bud scar numbers. Metabolomic analyses revealed changes in certain amino acids and increased NAD+ levels, suggesting metabolic shifts in aging cells. Gene expression studies further underlined these age-related metabolic changes. This innovative platform offers a high-throughput, non-invasive method for age-specific yeast cell fractionation, with potential applications in industries ranging from food and beverages to pharmaceuticals.

Energy substrate supplementation increases ATP levels and is protective to PD neurons

Alteration of mitochondrial metabolism by various mutations or toxins leads to various neurological conditions. Age-related changes in energy metabolism could also play the role of a trigger for neurodegenerative disorders. Nonetheless, it is not clear if restoration of ATP production or supplementation of brain cells with substrates for energy production could be neuroprotective. Using primary neurons and astrocytes, and neurons with familial forms of neurodegenerative disorders we studied whether various substrates of energy metabolism could improve mitochondrial metabolism and stimulate ATP production, and whether increased ATP levels could protect cells against glutamate excitotoxicity and neurodegeneration. We found that supplementation of neurons with several substrates, or combination thereof, for the TCA cycle and cellular respiration, and oxidative phosphorylation resulted in an increase in mitochondrial NADH level and in mitochondrial membrane potential and led to an increased level of ATP in neurons and astrocytes. Subsequently, these cells were protected against energy deprivation during ischemia or glutamate excitotoxicity. Provision of substrates for energy metabolism to cells with familial forms of Parkinson's disease also prevented triggering of cell death. Thus, restoration of energy metabolism and increase of ATP production can play neuroprotective role in neurodegeneration. A combination of a succinate salt of choline and nicotinamide provided the best results.

Age-Related Changes in Hepatic Lipid Metabolism and Abdominal Adipose Deposition in Yellow-Feathered Broilers Aged from 1 to 56 Days.

The objective of this study was to evaluate the age-related changes in hepatic lipid metabolism, adipocyte hyperplasia, hypertrophy, and lipid metabolism in the abdominal adipose tissue of yellow-feathered broilers. Blood, liver, and abdominal adipose samples were collected on days 1, 7, 14, 21, 28, 35, 42, 49, and 56. Body, liver, and abdominal weight increased (p < 0.05) with age-related changes. The triacylglycerol content peaked on day 14, and total cholesterol content peaked on day 56. The adipocyte diameter and area peaked on day 56, and total DNA content peaked on day 7. The age-related changes in hepatic lipogenesis-related gene (ChREBP, SREBP-1c, ACC, FAS, SCD1) expression mainly occurred during days 1 to 21, hepatic lipolysis-related gene (CPT1, LPL, ApoB) expression mainly occurred during days 1 to 14, and abdominal adipose-deposition-related gene (PPARα, CPT1, LPL, PPARγ, C/EBPβ) expression occurred during days 1 to 14. These results demonstrated a dynamic pattern of hepatic lipid metabolism and abdominal adipose deposition in yellow-feathered broilers, which provides practical strategies to regulate hepatic lipid metabolism and reduce abdominal adipose deposition in yellow-feathered broilers.

Immunosenescence and Inflammaging in COVID-19.

Despite knowledge gaps in understanding the full spectrum of the hyperinflammatory phase caused by SARS-CoV-2, according to the World Health Organization (WHO), COVID-19 is still the leading cause of death worldwide. Susceptible people to severe COVID-19 are those with underlying medical conditions or those with dysregulated and senescence-associated immune responses. As the immune system undergoes aging in the elderly, such drastic changes predispose them to various diseases and affect their responsiveness to infections, as seen in COVID-19. At-risk groups experience poor prognosis in terms of disease recovery. Changes in the quantity and quality of immune cell function have been described in numerous literature sites. Impaired immune cell function along with age-related metabolic changes can lead to features such as hyperinflammatory response, immunosenescence, and inflammaging in COVID-19. Inflammaging is related to the increased activity of the most inflammatory factors and is the main cause of age-related diseases and tissue failure in the elderly. Since hyperinflammation is a common feature of most severe cases of COVID-19, this pathway, which is not fully understood, leads to immunosenescence and inflammaging in some individuals, especially in the elderly and those with comorbidities. In this review, we shed some light on the age-related abnormalities of innate and adaptive immune cells and how hyperinflammatory immune responses contribute to the inflammaging process, leading to clinical deterioration. Further, we provide insights into immunomodulation-based therapeutic approaches, which are potentially important considerations in vaccine design for elderly populations.

Current Concepts of Molecular Mechanisms of Age-Related Changes in Eye Lens

Age-related cataract is the leading cause of vision loss in old people worldwide. According to the World Health Organization it accounts for 47.8 % of the total number of ocular pathologies in people over 50 years old. Despite the rapid development of cataract surgery technology, surgery remains a challenge due to its cost and the increasing number of patients. Literature review is devoted to current concepts of pathogenesis and molecular mechanisms of age-related changes in eye lens. There are the three main theories of cataractogenesis: oxidative stress; the impact of quinoid substances, which are formed due to the impairment of aromatic amino acid metabolism and the activation of aldo reductase enzyme with subsequent accumulation of sorbitol, reactive oxygen species (ROS) generation, dysfunction of Na+/K+ channels and calcium deregulation causing lens epithelial cells apoptosis. Theories of pathogenesis are linked and based on the development of age-related changes in protein metabolism (the majority of nuclear α-crystallins are insoluble), glucose metabolism (non-enzymatic glycosylation of proteins), lipid metabolism, enzyme activity and the loss of membrane potential of cells ( the increase of Na+ and Ca2+ level and the decrease of K+ level). Key element of all theories of age-related changes in eye lens is the aggregation of high molecular weight proteins covalent-bonded of disulfide linkages. Based on molecular mechanisms of cataractogenesis, the development of pathogenetically oriented medical methods of correction of the age-related changes in lens is carried on. This review provides information on results of experimental and clinical studies which demonstrate the anti-cataract effect of Pirenoxine 0, 005 %.

Gas-Phase Biosensors (Bio-Sniffers) for Measurement of 2-Nonenal, the Causative Volatile Molecule of Human Aging-Related Body Odor.

The molecule 2-nonenal is renowned as the origin of unpleasant human aging-related body odor that can potentially indicate age-related metabolic changes. Most 2-nonenal measurements rely on chromatographic analytical systems, which pose challenges in terms of daily usage and the ability to track changes in concentration over time. In this study, we have developed liquid- and gas-phase biosensors (bio-sniffers) with the aim of enabling facile and continuous measurement of trans-2-nonenal vapor. Initially, we compared two types of nicotinamide adenine dinucleotide (phosphate) [NAD(P)]-dependent enzymes that have the catalytic ability of trans-2-nonenal: aldehyde dehydrogenase (ALDH) and enone reductase 1 (ER1). The developed sensor quantified the trans-2-nonanal concentration by measuring fluorescence (excitation: 340 nm, emission: 490 nm) emitted from NAD(P)H that was generated or consumed by ALDH or ER1. The ALDH biosensor reacted to a variety of aldehydes including trans-2-nonenal, whereas the ER1 biosensor showed high selectivity. In contrast, the ALDH bio-sniffer showed quantitative characteristics for trans-2-nonenal vapor at a concentration range of 0.4-7.5 ppm (with a theoretical limit of detection (LOD) and limit of quantification (LOQ) of 0.23 and 0.26 ppm, respectively), including a reported concentration (0.85-4.35 ppm), whereas the ER1 bio-sniffer detected only 0.4 and 0.8 ppm. Based on these findings, headspace gas of skin-wiped alcohol-absorbed cotton collected from study participants in their 20s and 50s was measured by the ALDH bio-sniffer. Consequently, age-related differences in signals were observed, suggesting the potential for measuring trans-2-nonenal vapor.

Age-related changes in energy metabolism in peripheral mononuclear blood cells (PBMCs) and the brains of cognitively healthy seniors

Mitochondrial dysfunction is a hallmark of cellular senescence and many age-related neurodegenerative diseases. We therefore investigated the relationship between mitochondrial function in peripheral blood cells and cerebral energy metabolites in young and older sex-matched, physically and mentally healthy volunteers. Cross-sectional observational study involving 65 young (26.0 ± 0.49 years) and 65 older (71.7 ± 0.71 years) women and men recruited. Cognitive health was evaluated using established psychometric methods (MMSE, CERAD). Blood samples were collected and analyzed, and fresh peripheral blood mononuclear cells (PBMCs) were isolated. Mitochondrial respiratory complex activity was measured using a Clarke electrode. Adenosine triphosphate (ATP) and citrate synthase activity (CS) were determined by bioluminescence and photometrically. N-aspartyl-aspartate (tNAA), ATP, creatine (Cr), and phosphocreatine (PCr) were quantified in brains using 1H- and 31P-magnetic resonance spectroscopic imaging (MRSI). Levels of insulin-like growth factor 1 (IGF-1) were determined using a radio-immune assay (RIA). Complex IV activity (CIV) (− 15%) and ATP levels (− 11%) were reduced in PBMCs isolated from older participants. Serum levels of IGF-1 were significantly reduced (− 34%) in older participants. Genes involved in mitochondrial activity, antioxidant mechanisms, and autophagy were unaffected by age. tNAA levels were reduced (− 5%), Cr (+ 11%), and PCr (+ 14%) levels were increased, and ATP levels were unchanged in the brains of older participants. Markers of energy metabolism in blood cells did not significantly correlate with energy metabolites in the brain. Age-related bioenergetic changes were detected in peripheral blood cells and the brains of healthy older people. However, mitochondrial function in peripheral blood cells does not reflect energy related metabolites in the brain. While ATP levels in PBMCs may be be a valid marker for age-related mitochondrial dysfunction in humans, cerebral ATP remained constant.

Potentially Harmful Drug-Drug Interactions and Their Associated Factors Among Hospitalized Cardiac Patients: A Cross-Sectional Study.

Cardiovascular diseases are responsible for a significant proportion of mortalities worldwide. Elderly patients are the most affected by cardiovascular diseases, and because of factors such as polypharmacy, multimorbidity, and age-related changes in drug availability and metabolism, they are highly susceptible to the occurrence of drug-drug interactions. Drug-drug interactions are among the many drug-related problems leading to negative outcomes among inpatients and outpatients. Thus, it is important to investigate the prevalence, involved drugs, and factors related to potential drug-drug interactions (pDDIs) to properly optimize pharmacotherapy regimens for these patients. We aimed to determine the prevalence of pDDIs, drugs most frequently implicated, and significant predictors associated with these interactions among hospitalized patients in the Cardiology Unit at Sultan Qaboos University Hospital in Muscat, Oman. This retrospective cross-sectional study included 215 patients. Micromedex Drug-Reax® was used to identify pDDIs. Data extracted from patients' medical records were collected and analyzed. Univariable and multivariable linear regression was applied to determine the predictors associated with the observed pDDIs. A total of 2057 pDDIs were identified, with a median of nine (5-12) pDDIs per patient. Patients with at least one pDDI accounted for 97.2% of all the included patients. The majority of pDDIs were of major severity (52.6%), fair level of documentation (45.5%), and pharmacodynamic basis (55.9%). Potential drug-drug interactions between atorvastatin and clopidogrel were the most frequently observed (9%). Of all the detected pDDIs, around 79.6% of them included at least one antiplatelet drug. Having diabetes mellitus as a comorbidity (B = 2.564, p < 0.001) and the number of drugs taken during the hospitalization period (B = 0.562, p < 0.001) were factors positively associated with the frequency of pDDIs. Potential drug-drug interactions were highly prevalent among hospitalized cardiac patients at Sultan Qaboos University Hospital, Muscat, Oman. Patients having diabetes as a comorbidity and with a high number of administered drugs were at a higher risk of an increased number of pDDIs.

Methionine adenosyltransferase2A inhibition restores metabolism to improve regenerative capacity and strength of aged skeletal muscle

We investigate the age-related metabolic changes that occur in aged and rejuvenated myoblasts using in vitro and in vivo models of aging. Metabolic and signaling experiments reveal that human senescent myoblasts and myoblasts from a mouse model of premature aging suffer from impaired glycolysis, insulin resistance, and generate Adenosine triphosphate by catabolizing methionine via a methionine adenosyl-transferase 2A-dependant mechanism, producing significant levels of ammonium that may further contribute to cellular senescence. Expression of the pluripotency factor NANOG downregulates methionine adenosyltransferase 2 A, decreases ammonium, restores insulin sensitivity, increases glucose uptake, and enhances muscle regeneration post-injury. Similarly, selective inhibition of methionine adenosyltransferase 2 A activates Akt2 signaling, repairs pyruvate kinase, restores glycolysis, and enhances regeneration, which leads to significant enhancement of muscle strength in a mouse model of premature aging. Collectively, our investigation indicates that inhibiting methionine metabolism may restore age-associated impairments with significant gain in muscle function.

Abstract 63: Age-related Changes In Gray Matter Cerebral Metabolism And Vascular Reactivity In Children

Introduction: Metabolic demand changes throughout childhood as the brain develops, peaking in the 2 nd decade of life. Cerebral blood flow (CBF) is dynamic throughout childhood, likely in response to the increased metabolic demand of brain development. Cerebrovascular reactivity (CVR) reflects the ability to further increase CBF in response to a stimulus, such as carbon dioxide (CO 2 ). We hypothesized that gray matter oxygen metabolism (GM CMRO 2 ) is increased in younger children, corresponding to higher GM CBF and lower GM CVR. Methods: CVR was calculated as the proportional change of a subject’s MRI-measured blood oxygen level dependent signal in response to an increase in end-tidal CO 2 administered by the RespirAct® RA-MR™ device. GM CMRO 2 was calculated voxel-by-voxel as the product of GM CBF (arterial spin labeling), GM oxygen extraction fraction (asymmetric spin echo), and arterial oxygen content (= Hb х (oxygen saturation)х1.34). Univariate relationships were tested using Spearman’s correlation coefficient, and corrected for multiple comparisons. Results: GM CVR, CBF, and CMRO 2 were calculated for 15 healthy participants (ages 8-19, 7 male). GM CMRO 2 was highest in young children and decreased with age (ρ=-0.68, P=0.005), as did CBF (ρ =-0.67, P=0.006). CVR was lower in young children, increasing with age (ρ=0.58, P=0.02). However, while GM CVR correlated with CBF (ρ=-0.64, P=0.01) it did not significantly associate with CMRO 2 (ρ=-0.43, P=0.114). Conclusion: Although GM CMRO 2 and CVR both have age-related changes, CVR does not directly correlate with CMRO 2 . Rather, their relationship may be moderated through other influences on CBF, as further study will investigate. Figure: Linear fits and 95% confidence intervals of subject data, including age, GM CBF, and GM CMRO 2 , versus GM CVR. P-values are from Spearman’s test for monotonic correlation.

Possibilities of improving the effectiveness of treatment of manifestations of metabolic syndrome in the elderly (on the example of taurine)

The article presents modern data on the formation and manifestations of multiple metabolic disorders with an emphasis on the features of pathology in old age. Age-related changes in nutrition, physical activity, carbohydrate and lipid metabolism are additional risk factors for the development of metabolic syndrome and determine the high prevalence of this pathology in old age. Multiple metabolic disorders aggravate the course of each of them and worsen the prognosis due to high risks of cardiovascular and other types of mortality. Timely diagnosis and effective correction of metabolic syndrome manifestations will reduce these risks and increase life expectancy while improving its quality. In order to increase the effectiveness of basic therapy of metabolic disorders, the use of drugs capable of positively affecting multiple metabolic disorders has been shown. In particular, this paper provides an evidence base for the effectiveness of taurine in patients with metabolic syndrome. When using taurine in addition to basic standard therapy, there is a significant decrease in blood pressure, glucose levels, insulin, serum lipid spectrum, body mass index.

Anorexia of Aging: Metabolic Changes and Biomarker Discovery.

The age-associated decrease in appetite and food intake is referred to as "anorexia of aging". Older adults with anorexia show changes in the quantity/quality of energy supplied to the organism which eventually may cause a mismatch between ingested calories and physiological energy demands. Therefore, a state of malnutrition and impaired metabolism may ensue which renders older people more vulnerable to stressors and more prone to incur negative health outcomes. These latter cover a wide range of conditions including sarcopenia, low engagement in physical activity, and more severe consequences such as disability, loss of independence, hospitalization, nursing home placement, and mortality. Malnutrition has been recognized by the European Society of Clinical Nutrition (ESPEN) among the chief risk factors for the development of frailty. Frailty refers to a state of increased vulnerability to stressors stemming from reduced physiologic reserve, and according to ESPEN, is also nutrition-based. Alike frailty, anorexia is highly prevalent among older adults, and its multifactorial nature includes metabolic changes that develop in older age and possibly underly the condition. Circulating factors, including hormones (eg, cholecystokinin, ghrelin, leptin, and inflammatory and microbial mediators of gut dysbiosis), have been proposed as biomarkers for this condition to support early identification and develop personalized nutritional interventions. Additional studies are needed to untangle the interrelationship between gut microbiota and appetite regulation in older adults operating through brain-gut crosstalk. Furthermore, the contribution of the genetic background to appetite regulation and specific nutritional needs warrants investigation. Here, we provide an overview on anorexia of aging in the context of age-related metabolic changes. A special focus is placed on candidate biomarkers that may be used to assist in the early identification of anorexia of aging and in the development of personalized nutritional counseling.

Age-related metabolic and neurodegenerative changes in SAMP8 mice.

The most important risk factor for the development of sporadic Alzheimer’s disease (AD) is ageing. Senescence accelerated mouse prone 8 (SAMP8) is a model of sporadic AD, with senescence accelerated resistant mouse (SAMR1) as a control. In this study, we aimed to determine the onset of senescence-induced neurodegeneration and the related potential therapeutic window using behavioral experiments, immunohistochemistry and western blotting in SAMP8 and SAMR1 mice at 3, 6 and 9 months of age. The Y-maze revealed significantly impaired working spatial memory of SAMP8 mice from the 6th month. With ageing, increasing plasma concentrations of proinflammatory cytokines in SAMP8 mice were detected as well as significantly increased astrocytosis in the cortex and microgliosis in the brainstem. Moreover, from the 3rd month, SAMP8 mice displayed a decreased number of neurons and neurogenesis in the hippocampus. From the 6th month, increased pathological phosphorylation of tau protein at Thr231 and Ser214 was observed in the hippocampi of SAMP8 mice. In conclusion, changes specific for neurodegenerative processes were observed between the 3rd and 6th month of age in SAMP8 mice; thus, potential neuroprotective interventions could be applied between these ages.

Sensitive liquid chromatography/tandem mass spectrometry method for the simultaneous determination of seventeen beta blockers

In recent years, examples of drugs responsible for acute drug intoxication in elderly people include benzodiazepines, phenobarbital, digitalis preparations, phenytoin, beta blockers or calcium antagonists, and antidepressants in Japan. Due to the diversity of underlying diseases, the reasons for this include increasing number of prescription medicines due to regular oral medicines themselves interacting, and age-related changes in drug metabolism. Beta blockers for clinical use are employed in the management of a range of disorders, including hypertension, heart failure, arrhythmias, migraine headache and tremor. Beta blockers are prescribed widely and also have a high frequency of accidental ingestion by the elderly people. Cardiovascular drugs (beta blockers) present more serious symptoms of intoxication than the underlying diseases themselves. The aim of this study is to develop and validate a sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) with ESI method for the simultaneous determination of seventeen beta blockers (atenolol, carteolol, nadolol, pindolol, timolol, acebutolol, arotinolol, metoprolol, esmolol, celiprolol, labetalol, bisoprolol, propranolol, alprenolol, betaxolol, bevantolol and carvedilol). The extractions of beta blockers in human serum were performed by solid-phase extraction method using Oasis® PRiME HLB column (Waters). LC-MS/MS experiments were performed with a HPLC system, which consisted of Shimadzu LC-20AD pumps, a SIL-20AC autosampler and the 4000 QTRAP mass spectrometer (AB SCIEX). The chromatographic separation was performed on a Mightysil-RP-18 MS column (150 × 2.0-mm i.d., 5 μm). For the gradient elution, two solvents were used: (A) 10 mM acetic ammonium buffer and (B) acetonitrile. The flow rate was 0.20 mL/min and the column and autosampler were maintained at 37 and 4˚C, respectively. The settings of the turbo ion-spray were as follows; curtain gas, N2:40 psi, collision gas, N2:4 psi, collision energy: 27∼41 V, ion-spray voltage: 5500 V, ionization mode: ESI positive, source temperature: 600˚C. Separation and sensitivity for the detection of seventeen beta blockers by LC-MS/MS were sufficient and the precursor [M + H]+ ion was detected in the mass spectrum for each drug. This method had a chromatographic total run time of 15 min. The calibration curves were linear over the concentration range of 20–400 ng/mL for seventeen beta blockers (r = 0.9686∼0.9997). The extraction yields of human serum sample with Oasis® PRiME HLB column were ranged from 66.1 to 93.5%, the precision within 0.07 CV values were acceptable of this method. But the extraction yields of bevantlol (37.5%) and carvedilol (26.2%) were low. Currently, we are experimenting to improve the extraction yields of bevantolol and carvedilol. Phyo Lwin EM, et al (2017, Bioanalysis.) developed a method for the determination of atenolol in human plasma and milk sample by LC-MS/MS. The limits of detection (LOD) and quantification (LOQ) were in the range 1.0 ng/mL and 5.0 ng/mL for atenolol. Our LC-MS/MS with ESI method was able to measure compounds at approximately the same concentrations as the analytical methods of Phyo Lwin EM, et al. In our experiments, LOD and LOQ in the range 0.0034–1.6 ng/mL and were 20 ng/mL for seventeen beta blockers. The presently established method is very useful for simultaneous measurements of beta blockers in human serum by LC-MS/MS in clinical and forensic investigations.